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Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain.
ACS Chem Neurosci. 2018 07 18; 9(7):1552-1559.AC

Abstract

Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins, which are involved in immune regulation, vascular function, and synaptic signaling. COX-2 also inactivates the endogenous cannabinoid (eCB) 2-arachidonoylglycerol (2-AG) via oxygenation of its arachidonic acid backbone to form a variety of prostaglandin glyceryl esters (PG-Gs). Although this oxygenation reaction is readily observed in vitro and in intact cells, detection of COX-2-derived 2-AG oxygenation products has not been previously reported in neuronal tissue. Here we show that 2-AG is metabolized in the brain of transgenic COX-2-overexpressing mice and mice treated with lipopolysaccharide to form multiple species of PG-Gs that are detectable only when monoacylglycerol lipase is concomitantly blocked. Formation of these PG-Gs is prevented by acute pharmacological inhibition of COX-2. These data provide evidence that neuronal COX-2 is capable of oxygenating 2-AG to form a variety PG-Gs in vivo and support further investigation of the physiological functions of PG-Gs.

Authors

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Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29722963

Citation

Morgan, Amanda J., et al. "Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain." ACS Chemical Neuroscience, vol. 9, no. 7, 2018, pp. 1552-1559.
Morgan AJ, Kingsley PJ, Mitchener MM, et al. Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain. ACS Chem Neurosci. 2018;9(7):1552-1559.
Morgan, A. J., Kingsley, P. J., Mitchener, M. M., Altemus, M., Patrick, T. A., Gaulden, A. D., Marnett, L. J., & Patel, S. (2018). Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain. ACS Chemical Neuroscience, 9(7), 1552-1559. https://doi.org/10.1021/acschemneuro.7b00499
Morgan AJ, et al. Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain. ACS Chem Neurosci. 2018 07 18;9(7):1552-1559. PubMed PMID: 29722963.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Detection of Cyclooxygenase-2-Derived Oxygenation Products of the Endogenous Cannabinoid 2-Arachidonoylglycerol in Mouse Brain. AU - Morgan,Amanda J, AU - Kingsley,Philip J, AU - Mitchener,Michelle M, AU - Altemus,Megan, AU - Patrick,Toni A, AU - Gaulden,Andrew D, AU - Marnett,Lawrence J, AU - Patel,Sachin, Y1 - 2018/05/09/ PY - 2018/5/4/pubmed PY - 2019/10/1/medline PY - 2018/5/4/entrez KW - Endocannabinoid KW - Lumiracoxib KW - cannabinoid KW - lipopolysaccharide KW - monoacylglycerol lipase KW - prostaglandin glyceryl esters KW - prostamide SP - 1552 EP - 1559 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 9 IS - 7 N2 - Cyclooxygenase-2 (COX-2) catalyzes the formation of prostaglandins, which are involved in immune regulation, vascular function, and synaptic signaling. COX-2 also inactivates the endogenous cannabinoid (eCB) 2-arachidonoylglycerol (2-AG) via oxygenation of its arachidonic acid backbone to form a variety of prostaglandin glyceryl esters (PG-Gs). Although this oxygenation reaction is readily observed in vitro and in intact cells, detection of COX-2-derived 2-AG oxygenation products has not been previously reported in neuronal tissue. Here we show that 2-AG is metabolized in the brain of transgenic COX-2-overexpressing mice and mice treated with lipopolysaccharide to form multiple species of PG-Gs that are detectable only when monoacylglycerol lipase is concomitantly blocked. Formation of these PG-Gs is prevented by acute pharmacological inhibition of COX-2. These data provide evidence that neuronal COX-2 is capable of oxygenating 2-AG to form a variety PG-Gs in vivo and support further investigation of the physiological functions of PG-Gs. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/29722963/Detection_of_Cyclooxygenase_2_Derived_Oxygenation_Products_of_the_Endogenous_Cannabinoid_2_Arachidonoylglycerol_in_Mouse_Brain_ L2 - https://doi.org/10.1021/acschemneuro.7b00499 DB - PRIME DP - Unbound Medicine ER -